Mohammed T. Abou-Saleh

NEUROPATHOLOGY: OTHER DEMENTIAS 261cerebral cortex showed 21–29% loss of substance, the cerebralwhite matter 29–34% and the thalamus 28% in one study 60 , butcortical abnormalities may be very difficult to identify 49 .Neuronal loss has been identified in the superior frontal andcingulate cortices, particularly of laminae III and V pyramidalneurones, but this does not seem to correlate with severity ofstriatal pathology, suggesting that it is a primary part of thedisease process 61 .However, another study 62 found evidence of loss of largepyramidal neurones from laminae III, V and VI of theprefrontal cortex, which was most severe in pathologicalgrade 4 HD, and suggested that this represented retrogradedegeneration of cortical glutamatergic neurones. Nerve cell lossfrom specific regions of the entorhinal cortex and subiculumhas also been reported 63 .There is controversy over whether neuronal loss in thesubstantia nigra does 64 or does not 65 occur in HD. Preservationof neuronal populations in the nucleus basalis of Meynert, locuscoeruleus and dorsal raphe nuclei has also been reported, leadingto the suggestion that dementia in HD may be due not to damageto subcortical nuclei, as in the other ‘‘subcortical’’ dementias, butto failure of ascending systems within the basal ganglia orneuronal loss in the cerebral cortex 65 .FRONTOTEMPORAL DEMENTIAThe frontotemporal dementias (FTD) are non-Alzheimer formsof dementia characterized clinically by behavioural and personalitychange leading to apathy and mutism, and by progressiveatrophy of the frontal, anterior parietal and anterior temporallobes. The histology is variable and defines three separatesubgroups 66 :. Frontal lobe degeneration. This is characterized by microvacuolardegeneration, gliosis and neuronal loss, principallyaffecting laminae II and III.. Pick’s disease (FTD with Pick-type histology) is represented bytranscortical neuronal loss, gliosis and cavitation, togetherwith the presence of tau and ubiquitin-positive intraneuronalinclusions (Pick bodies) and aB crystallin-positive balloonedneurones (Pick cells). Although there is overlap between Pick’sdisease and other forms of FTD, as well as with corticobasaldegeneration, the distinctive distribution of the pathologicalchanges—such as the involvement of the dentate fascia by Pickbodies—has led some authors to regard Pick’s disease as aunique disease rather than a histological variant within theFTD spectrum 67 . However, both of these different histologiescan have a variable topographical distribution in the brain,producing progressive language disorder when both temporallobes are involved or the disease primarily affects the lefthemisphere, or progressive apraxia when parietal and motorareas are involved 66 .. Motor neurone disease inclusion dementia. Either of thesehistologies can overlap with classical motor neurone disease,either as a dementing disorder occurring in patients known tohave MND, or also as an identical histology occurring inpatients without motor dysfunction 66,68 .Fifty-eight percent of cases of FTD show a previous familyhistory of a similar disorder, and linkage to chromosome 17 hasbeen established in some families. Following the current trend for‘‘molecular’’ classification of the dementias, the various forms ofFTD have sometimes been described as ‘‘tauopathies’’ but 64%cases of FTD in one study showed no intracellular tau-positiveinclusions 69 . This is an area where further study and clarificationis required.OTHER DISORDERSMany other disorders may be associated with dementia in theelderly, including progressive supranuclear palsy 70 and, occasionally,multiple sclerosis 71 . There are also a number of raredementing disorders of uncertain nosological status, such as thetangle-predominant form of dementia 72 and argyrophilic graindisease 73 .This section of the book would not be complete without thereader being reminded of the estimated 13.2% 72 of causes ofdementia in the elderly—including intracranial space-occupyinglesions, particularly chronic subdural haematoma; metabolicdisorders, such as hypothyroidism and hypopituitarism 75 ;and ‘‘normal-pressure’’ hydrocephalus—that are potentiallytreatable 76 .REFERENCES1. Esiri MM, Hyman BT, Bayreuther K, Masters CL. Ageing anddementia. In Graham DI, Lantos PL, eds, Greenfield’sNeuropathology 6th edn, vol II. London: Arnold, 1997; 172–3.2. Jellinger K, Danielczyk W, Fischer P, Gabriel E. Clinicopathologicalanalysis of dementia disorders in the elderly. J Neurol Sci 1990; 95:239–58.3. McKeith IG, Galasko D, Kosaka K et al. 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